BET3 encodes a novel hydrophilic protein that acts in conjunction with yeast SNAREs.

Rossi, Guendalina; Kolstad, Kaare; Stone, Shelly; Palluault, F; Ferro‐Novick, Susan

doi:10.1091/mbc.6.12.1769

Cited by 66 publications

(81 citation statements)

References 36 publications

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“…The complex process may require an intermolecular regulatory role in addition to the intramolecular regulation of SNARE domains in the formation of the core complexes. Bet3p, a component of TRAPP, was shown to interact genetically with yeast SNAREs and is required for vesicle targeting and fusion (37). SEDL, as a component of human TRAPP, may be responsible for the interaction with a SNARE protein.…”

Section: Resultsmentioning

confidence: 99%

Crystal Structure of SEDL and Its Implications for a Genetic Disease Spondyloepiphyseal Dysplasia Tarda

Jang

Kim

Cho

et al. 2002

Journal of Biological Chemistry

100

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SEDL is an evolutionarily highly conserved protein in eukaryotic organisms. Deletions or point mutations in the SEDL gene are responsible for the genetic disease spondyloepiphyseal dysplasia tarda (SEDT), an X-linked skeletal disorder. SEDL has been identified as a component of the transport protein particle (TRAPP), critically involved in endoplasmic reticulum-to-Golgi vesicle transport. Herein, we report the 2.4 Å resolution structure of SEDL, which reveals an unexpected similarity to the structures of the N-terminal regulatory domain of two SNAREs, Ykt6p and Sec22b, despite no sequence homology to these proteins. The similarity and the presence of unusually many solvent-exposed apolar residues of SEDL suggest that it serves regulatory and/or adaptor functions through multiple protein-protein interactions. Of the four known missense mutations responsible for SEDT, three mutations (S73L, F83S, V130D) map to the protein interior, where the mutations would disrupt the structure, and the fourth (D47Y) on a surface at which the mutation may abrogate functional interactions with a partner protein.Intracellular targeting and fusion of transport vesicles in eukaryotes are tightly regulated to avoid inappropriate mixing of the contents in different compartments. Central components of the membrane fusion are the proteins denoted as SNAREs 1 (soluble N-ethylmaleimide-sensitive factor attachment receptor proteins). SNAREs constitute a superfamily of proteins that share a highly conserved sequence motif, the SNARE motif composed of 60 -70 amino acids (1). Most SNAREs are membrane proteins anchored on vesicular carriers (v-SNARE) and target organelles (t-SNARE) (1). Association of the SNARE domains between v-and t-SNAREs to form a helical bundle, termed the core complex (2), is believed to be the prime event that drives membrane fusion (3, 4). While the specific pairing of v-and t-SNAREs is one mechanism of providing the fidelity of membrane fusion, other proteins or protein complexes such as the transport protein particle (TRAPP) are known to provide further specificity by controlling the tethering process, in which a transport vesicle is properly docked on target membrane prior to pairing of SNAREs (5). TRAPP is localized to an early Golgi compartment (6) and is able to exchange the nucleotide of Ypt1p GTPase, which is an upstream event of v-and t-SNARE interactions (7,8). Recent in vitro transport studies showed that yeast TRAPP I binds COPII, the vesicle coat derived from the endoplasmic reticulum (ER), indicating that TRAPP I is the receptor for tethering COPII vesicles to Golgi membranes (6). The TRAPP complexes (TRAPP I and TRAPP II) are composed of 7-10 different polypeptides, which are highly conserved in evolution, with the yeast subunits sharing between 29 and 54% sequence identity with their human counterparts (9). The biochemical function of any of the constituent proteins is virtually unknown, although the TRAPP complex was shown to stimulate nucleotide exchange on the Ypt1p and the Ypt31/32 GTPases (10).Spond...

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Section: Resultsmentioning

confidence: 99%

Crystal Structure of SEDL and Its Implications for a Genetic Disease Spondyloepiphyseal Dysplasia Tarda

Jang

Kim

Cho

et al. 2002

Journal of Biological Chemistry

100

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“…In addition to the extended structure of Uso1, which is predicted to span a distance of .180 nm (Yamakawa et al 1996), the multisubunit TRAPPI complex is required for COPII-dependent transport to Golgi acceptor membranes (Rossi et al 1995;Sacher et al 1998). In vitro assays revealed that TRAPPI can also function to physically link COPII vesicles to Golgi membranes (Sacher et al 2001).…”

Section: Vesicle Tetheringmentioning

confidence: 99%

Secretory Protein Biogenesis and Traffic in the Early Secretory Pathway

2013

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The secretory pathway is responsible for the synthesis, folding, and delivery of a diverse array of cellular proteins. Secretory protein synthesis begins in the endoplasmic reticulum (ER), which is charged with the tasks of correctly integrating nascent proteins and ensuring correct post-translational modification and folding. Once ready for forward traffic, proteins are captured into ER-derived transport vesicles that form through the action of the COPII coat. COPII-coated vesicles are delivered to the early Golgi via distinct tethering and fusion machineries. Escaped ER residents and other cycling transport machinery components are returned to the ER via COPI-coated vesicles, which undergo similar tethering and fusion reactions. Ultimately, organelle structure, function, and cell homeostasis are maintained by modulating protein and lipid flux through the early secretory pathway. In the last decade, structural and mechanistic studies have added greatly to the strong foundation of yeast genetics on which this field was built. Here we discuss the key players that mediate secretory protein biogenesis and trafficking, highlighting recent advances that have deepened our understanding of the complexity of this conserved and essential process. TABLE OF CONTENTS Abstract 383Introduction 384

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“…The Bet3 protein is an essential component of the trafficking protein particle (TRAPP) complex (Menon et al, 2006), which, together with SNAREs and Rab-GTPases (Kim et al, 2005;Loh et al, 2005;Rossi et al, 1995;Sacher et al, 2008), is involved in vesicular transport in eukaryotic cells. We report here that NS5A from BVDV interacts physically with NIBP and inhibits NF-kB activation, which may play a role in BVDV pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Bovine viral diarrhea virus non-structural protein 5A interacts with NIK- and IKKβ-binding protein

Zahoor

Yamane

Mohamed

et al. 2010

Journal of General Virology

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Bovine viral diarrhea virus (BVDV) is a positive-sense, single-stranded RNA virus that causes an economically important livestock disease worldwide. Previous studies have suggested that nonstructural protein 5A (NS5A) from hepatitis C virus (HCV) and BVDV plays a similar role during virus infection. Extensive reports are available on HCV NS5A and its interactions with the host cellular proteins; however, the role of NS5A during BVDV infection remains largely unclear. To identify the cellular proteins that interact with the N terminus of NS5A and could be involved in its function, we conducted a yeast two-hybrid screening. As a result, we identified a cellular protein termed bovine NIK-and IKKb-binding protein (NIBP), which is involved in protein trafficking and nuclear factor kappa B (NF-kB) signalling in cells. The interaction of NS5A with NIBP was confirmed both in vitro and in vivo. Complementing our glutathione S-transferase pull-down and immunoprecipitation data are the confocal immunofluorescence results, which indicate that NS5A colocalized with NIBP on the endoplasmic reticulum in the cytoplasm of BVDV-infected cells. Moreover, the minimal residues of NIBP that interact with NS5A were mapped as aa 597-623. In addition, overexpression of NS5A inhibited NF-kB activation in HEK293 and LB9.K cells as determined by luciferase reporter-gene assay. We further showed that inhibition of endogenous NIBP by small interfering RNA molecules enhanced virus replication, indicating the importance of NIBP implications in BVDV pathogenesis. Being the first reported interaction between NIBP and a viral protein, this finding suggests a novel mechanism whereby viruses may subvert host-cell machinery for mediating trafficking as well as NF-kB signalling. INTRODUCTIONPestiviruses are important livestock pathogens that belong to the family Flaviviridae, which also includes the closely related genera Hepacivirus (Hepatitis C virus; HCV) and Flavivirus (Yellow fever virus and West Nile virus). The genus Pestivirus includes the species Bovine viral diarrhea virus 1 (BVDV-1), BVDV-2, Border disease virus and Classical swine fever virus. As a well-characterized prototype member of the genus Pestivirus within the family Flaviviridae, BVDV sometimes serves as a surrogate model for HCV life-cycle studies. BVDV is an enveloped virus containing a single, positive-sense RNA of approximately 12.3 kb. The genomic RNA consists of one long open reading frame (ORF), which is flanked by untranslated regions at both ends. The ORF encodes a single polyprotein of about 4000 aa, which is processed co-and posttranslationally by both viral and cellular proteases into at least 11 mature viral proteins (N pro , C, E rns , E1, E2, p7, NS2-3, NS4A, NS4B, NS5A and NS5B) (Lindenbach et al., 2007).BVDV non-structural protein 5A (NS5A) is a phosphoprotein of 56-58 kDa that plays an essential role in BVDV replication (Tellinghuisen et al., 2006) and shares many features with its counterpart HCV NS5A, e.g. both proteins are phosphorylated by the same or simila...

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BET3 encodes a novel hydrophilic protein that acts in conjunction with yeast SNAREs.

Cited by 66 publications

References 36 publications

Crystal Structure of SEDL and Its Implications for a Genetic Disease Spondyloepiphyseal Dysplasia Tarda

Crystal Structure of SEDL and Its Implications for a Genetic Disease Spondyloepiphyseal Dysplasia Tarda

Secretory Protein Biogenesis and Traffic in the Early Secretory Pathway

Bovine viral diarrhea virus non-structural protein 5A interacts with NIK- and IKKβ-binding protein

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